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Related Concept Videos

Brain Imaging01:14

Brain Imaging

272
Brain imaging technologies provide critical insights into both the structure and function of the human brain, enabling medical professionals and researchers to diagnose, study, and treat neurological disorders or psychiatric disorders more effectively.
These technologies include computerized axial tomography (CAT or CT scans), positron-emission tomography (PET scans),  magnetic resonance imaging (MRI),  functional magnetic resonance imaging (fMRI), and Transcranial Magnetic...
272

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Pretargeted imaging beyond the blood-brain barrier.

Vladimir Shalgunov1, Sara Lopes van den Broek1, Ida Vang Andersen1

  • 1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Universitetsparken 2 2100 Copenhagen Denmark umberto.battisti@sund.ku.dk matthias.herth@sund.ku.dk.

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|March 27, 2023
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Summary

We developed novel fluorine-18 labeled tetrazines for pretargeted imaging beyond the blood-brain barrier. This breakthrough enables in vivo imaging of brain targets, advancing neuroimaging and diagnostics.

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Area of Science:

  • Nuclear medicine
  • Bioorthogonal chemistry
  • Neuroimaging

Background:

  • Pretargeting enhances imaging contrast and reduces radiation dose.
  • Tetrazine ligation with trans-cyclooctene is a key bioorthogonal reaction.
  • Pretargeted imaging beyond the blood-brain barrier (BBB) remains a significant challenge.

Purpose of the Study:

  • To develop novel fluorine-18 labeled tetrazines for pretargeted imaging beyond the BBB.
  • To enable in vivo bioorthogonal reactions within the brain.
  • To establish a foundation for pretargeted neuroimaging of currently inaccessible targets.

Main Methods:

  • Rational drug design incorporating BBB penetration, contrast, and metabolism parameters.
  • Synthesis and evaluation of 18F-labeled tetrazines.
  • In vivo testing of tetrazine ligation efficiency with trans-cyclooctene in the brain.

Main Results:

  • Five 18F-labeled tetrazines demonstrated in vivo click performance in the brain.
  • [18F]18 exhibited the most favorable characteristics for brain pretargeting.
  • The lead compound [18F]18 is suitable for future pretargeted neuroimaging studies.

Conclusions:

  • Pretargeting beyond the BBB is achievable with 18F-labeled tetrazines.
  • This approach opens avenues for imaging soluble protein oligomers and other neurodegeneration biomarkers.
  • Enables early diagnosis, personalized treatment monitoring, and accelerated drug development in neurology.